EP3744775A1 - Blutvorratsbehälter aus polyvinylchlorid und gemischten weichmachern - Google Patents

Blutvorratsbehälter aus polyvinylchlorid und gemischten weichmachern Download PDF

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Publication number
EP3744775A1
EP3744775A1 EP20177110.2A EP20177110A EP3744775A1 EP 3744775 A1 EP3744775 A1 EP 3744775A1 EP 20177110 A EP20177110 A EP 20177110A EP 3744775 A1 EP3744775 A1 EP 3744775A1
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EP
European Patent Office
Prior art keywords
mixture
plasticizers
storage container
blood storage
flexible
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Pending
Application number
EP20177110.2A
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English (en)
French (fr)
Inventor
Craig L. Sandford
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Fenwal Inc
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Fenwal Inc
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Publication date
Application filed by Fenwal Inc filed Critical Fenwal Inc
Publication of EP3744775A1 publication Critical patent/EP3744775A1/de
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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61J—CONTAINERS SPECIALLY ADAPTED FOR MEDICAL OR PHARMACEUTICAL PURPOSES; DEVICES OR METHODS SPECIALLY ADAPTED FOR BRINGING PHARMACEUTICAL PRODUCTS INTO PARTICULAR PHYSICAL OR ADMINISTERING FORMS; DEVICES FOR ADMINISTERING FOOD OR MEDICINES ORALLY; BABY COMFORTERS; DEVICES FOR RECEIVING SPITTLE
    • A61J1/00—Containers specially adapted for medical or pharmaceutical purposes
    • A61J1/14—Details; Accessories therefor
    • A61J1/1468—Containers characterised by specific material properties
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
    • A01N1/00—Preservation of bodies of humans or animals, or parts thereof
    • A01N1/02—Preservation of living parts
    • A01N1/0236—Mechanical aspects
    • A01N1/0263—Non-refrigerated containers specially adapted for transporting or storing living parts whilst preserving, e.g. cool boxes, blood bags or "straws" for cryopreservation
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61J—CONTAINERS SPECIALLY ADAPTED FOR MEDICAL OR PHARMACEUTICAL PURPOSES; DEVICES OR METHODS SPECIALLY ADAPTED FOR BRINGING PHARMACEUTICAL PRODUCTS INTO PARTICULAR PHYSICAL OR ADMINISTERING FORMS; DEVICES FOR ADMINISTERING FOOD OR MEDICINES ORALLY; BABY COMFORTERS; DEVICES FOR RECEIVING SPITTLE
    • A61J1/00—Containers specially adapted for medical or pharmaceutical purposes
    • A61J1/05—Containers specially adapted for medical or pharmaceutical purposes for collecting, storing or administering blood, plasma or medical fluids ; Infusion or perfusion containers
    • A61J1/10—Bag-type containers
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61J—CONTAINERS SPECIALLY ADAPTED FOR MEDICAL OR PHARMACEUTICAL PURPOSES; DEVICES OR METHODS SPECIALLY ADAPTED FOR BRINGING PHARMACEUTICAL PRODUCTS INTO PARTICULAR PHYSICAL OR ADMINISTERING FORMS; DEVICES FOR ADMINISTERING FOOD OR MEDICINES ORALLY; BABY COMFORTERS; DEVICES FOR RECEIVING SPITTLE
    • A61J1/00—Containers specially adapted for medical or pharmaceutical purposes
    • A61J1/14—Details; Accessories therefor
    • A61J1/1475—Inlet or outlet ports
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B32—LAYERED PRODUCTS
    • B32B—LAYERED PRODUCTS, i.e. PRODUCTS BUILT-UP OF STRATA OF FLAT OR NON-FLAT, e.g. CELLULAR OR HONEYCOMB, FORM
    • B32B27/00—Layered products comprising a layer of synthetic resin
    • B32B27/06—Layered products comprising a layer of synthetic resin as the main or only constituent of a layer, which is next to another layer of the same or of a different material
    • B32B27/08—Layered products comprising a layer of synthetic resin as the main or only constituent of a layer, which is next to another layer of the same or of a different material of synthetic resin
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B32—LAYERED PRODUCTS
    • B32B—LAYERED PRODUCTS, i.e. PRODUCTS BUILT-UP OF STRATA OF FLAT OR NON-FLAT, e.g. CELLULAR OR HONEYCOMB, FORM
    • B32B27/00—Layered products comprising a layer of synthetic resin
    • B32B27/30—Layered products comprising a layer of synthetic resin comprising vinyl (co)polymers; comprising acrylic (co)polymers
    • B32B27/304—Layered products comprising a layer of synthetic resin comprising vinyl (co)polymers; comprising acrylic (co)polymers comprising vinyl halide (co)polymers, e.g. PVC, PVDC, PVF, PVDF
    • C—CHEMISTRY; METALLURGY
    • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08K—Use of inorganic or non-macromolecular organic substances as compounding ingredients
    • C08K5/00—Use of organic ingredients
    • C08K5/04—Oxygen-containing compounds
    • C08K5/10—Esters; Ether-esters
    • C08K5/11—Esters; Ether-esters of acyclic polycarboxylic acids
    • C—CHEMISTRY; METALLURGY
    • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08K—Use of inorganic or non-macromolecular organic substances as compounding ingredients
    • C08K5/00—Use of organic ingredients
    • C08K5/04—Oxygen-containing compounds
    • C08K5/10—Esters; Ether-esters
    • C08K5/12—Esters; Ether-esters of cyclic polycarboxylic acids
    • C—CHEMISTRY; METALLURGY
    • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08L—COMPOSITIONS OF MACROMOLECULAR COMPOUNDS
    • C08L27/00—Compositions of homopolymers or copolymers of compounds having one or more unsaturated aliphatic radicals, each having only one carbon-to-carbon double bond, and at least one being terminated by a halogen; Compositions of derivatives of such polymers
    • C08L27/02—Compositions of homopolymers or copolymers of compounds having one or more unsaturated aliphatic radicals, each having only one carbon-to-carbon double bond, and at least one being terminated by a halogen; Compositions of derivatives of such polymers not modified by chemical after-treatment
    • C08L27/04—Compositions of homopolymers or copolymers of compounds having one or more unsaturated aliphatic radicals, each having only one carbon-to-carbon double bond, and at least one being terminated by a halogen; Compositions of derivatives of such polymers not modified by chemical after-treatment containing chlorine atoms
    • C08L27/06—Homopolymers or copolymers of vinyl chloride
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B32—LAYERED PRODUCTS
    • B32B—LAYERED PRODUCTS, i.e. PRODUCTS BUILT-UP OF STRATA OF FLAT OR NON-FLAT, e.g. CELLULAR OR HONEYCOMB, FORM
    • B32B2439/00—Containers; Receptacles
    • B32B2439/40—Closed containers
    • B32B2439/46—Bags
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B32—LAYERED PRODUCTS
    • B32B—LAYERED PRODUCTS, i.e. PRODUCTS BUILT-UP OF STRATA OF FLAT OR NON-FLAT, e.g. CELLULAR OR HONEYCOMB, FORM
    • B32B2439/00—Containers; Receptacles
    • B32B2439/80—Medical packaging
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B32—LAYERED PRODUCTS
    • B32B—LAYERED PRODUCTS, i.e. PRODUCTS BUILT-UP OF STRATA OF FLAT OR NON-FLAT, e.g. CELLULAR OR HONEYCOMB, FORM
    • B32B2535/00—Medical equipment, e.g. bandage, prostheses, catheter

Definitions

  • the present disclosure is directed to containers for the storage of blood or blood components. More particularly, the present disclosure is directed to flexible containers that are made in whole or in part of polyvinyl chloride (or a non-PVC polyolefin blend) and a mixture of at least two plasticizers. Even more particularly, the present disclosure is directed to flexible containers wherein the mixture of plasticizers exhibit a controlled leaching and suppress hemolysis in the blood cells stored therein.
  • red blood cells may be administered to a patient suffering from a loss of blood due to trauma, as a post-chemotherapy treatment, or as part of a treatment of one or more blood borne diseases, such as certain anemias and the like.
  • RBCs Unless administered immediately after collection from a donor, RBCs must typically be stored for some period of time prior to transfusion. The storage period may be anywhere from a few days to several weeks.
  • Prolonged storage of RBCs can (negatively) affect RBC function.
  • RBCs In order for the RBCs to be suitable for transfusion to the recipient, RBCs must maintain adequate cell function and metabolism. For example, RBCs must maintain an adequate concentration of adenosine triphosphate (ATP) and 2, 3-DPG. In addition, the presence of lactate must not be too high in the stored RBCs. Still further, stored RBCs must have acceptably low levels of hemolysis. Hemolysis refers to the rupturing of the RBC membrane, believed to be caused by the oxidation of phospholipids in the cell membrane. Typically, an acceptable level of hemolysis is below 1.0% (in, for example, the U.S.) and 0.8% (in Europe) after 42 day storage. More preferably, an acceptable level of hemolysis in stored RBCs may be below 0.4%.
  • a sealed container usually made of a plastic (polymeric) material.
  • the containers approved for the collection of whole blood and the storage of RBCs are made of a polyvinyl chloride (PVC).
  • PVC polyvinyl chloride
  • a plasticizer is typically incorporated into the PVC.
  • a currently known and used plasticizer for medical grade PVC is di-ethylhexyl phthalate ester or DEHP.
  • DEHP di-ethylhexyl phthalate ester
  • Other plasticizers that have been used with PVC or other polyolefin materials include TEHTM, and the family of citrate esters described in U.S. Patent No. 5,026,347 .
  • plasticizers may have a beneficial effect on the storage life of RBCs. More particularly, plasticizers such as DEHP have been found to suppress hemolysis of RBCs stored in containers that include such leachable plasticizers. More recently, certain non-DEHP plasticizers have been found to provide hemolysis suppression in RBCs.
  • DEHP plasticizers
  • non-DEHP plasticizers have been found to provide hemolysis suppression in RBCs.
  • U.S. Patent No. 9,993,389 discloses plastic containers plasticized with 1,2 -cyclohexanedicarboxylic acid diisononyl ester (or DINCH), a leachable plasticizer, for the storage of red blood cells with acceptable hemolysis levels.
  • U.S. Patent Publication No. 2014/0276527 discloses plastic containers plasticized with di-2-ethylhexyl terephthalate ester, also a leachable plasticizer.
  • US Publication No. 2017/0172847 discloses the previously mentioned DINCH and DEHT esters as well as certain citrate esters that may be suitable plasticizers for PVC containers for the storage of blood components, such as RBCs.
  • the present disclosure is directed to polymeric compositions useful in the manufacture of containers for the storage of blood components.
  • the polymeric compositions include two or more primary plasticizers in a mixture that provides a controlled leaching of the plasticizers from the container wall surface and suppresses the hemolysis of red blood cells.
  • Different mixed primary plasticizer systems may be used in the polymeric composition and the containers made therefrom.
  • the term "primary plasticizer” excludes epoxidized oils but includes all other fluids that effect the glass transition of the PVC.
  • the present disclosure is directed to a flexible blood storage container comprising a pair of walls defining an interior chamber and at least one access port.
  • the container is made of a polymeric material including polyvinyl chloride and a mixture of at least two extractable primary plasticizers including at least about 78% (of the total primary plasticizer content) 1, 2 cyclohexanedicarboxyylic acid diisononyl ester and up to about 22% (of the total primary plasticizer content) acetyl tri-n-butyl citrate.
  • the present disclosure is directed to a flexible blood storage container including a pair of walls defining an interior chamber and at least one access port.
  • the container is made of a polymeric material including polyvinyl chloride and a mixture of least two extractable primary plasticizers including at least about 75% (of the total primary plasticizer content) di-2-ethylhexyl terephthalate ester and up to about 25%(of the total primary plasticizer content) acetyl tri-n-butyl citrate .
  • the stated percentages represent the percentage of the plasticizer present based on the total primary plasticizer content).
  • the present disclosure is directed to a flexible blood storage container including a pair of walls defining an interior chamber and at least one access port.
  • the container is made of a polymeric material including polyvinyl chloride and a mixture of least two extractable primary plasticizers 1, 2 cyclohexanedicarboxyylic acid diisononyl ester di-2-ethylhexyl terephthalate ester.
  • the present disclosure is directed to a flexible blood storage container including a pair of walls defining an interior chamber and at least one access port.
  • the container is made of a polymeric material including polyvinyl chloride and a mixture of least two extractable primary plasticizers comprising di-2-ethylhexyl terephthalate ester and acetyl tri-n-hexyl citrate.
  • the present disclosure is directed to a flexible blood storage container including a pair of walls defining an interior chamber and at least one access port.
  • the container is made of a polymeric material comprising polyvinyl chloride and a mixture of least two extractable primary plasticizers including di-2-ethylhexyl terephthalate ester and butyl tri-n- hexyl citrate.
  • containers described herein may be suitable for the long term storage of RBCs or for the collection and storage of whole blood or other components such as platelets and plasma.
  • containers for storing the RBC compositions disclosed herein are made of a polymeric material.
  • the containers may be permeable to oxygen or at least semi-permeable to oxygen.
  • container 10 may include one or more container walls 12 which define an interior chamber 15 for receiving the blood or blood component 20.
  • two sheets made of a polymeric material such as PVC plasticized in accordance with the mixed plasticizer systems disclosed herein
  • RF heat sealing
  • Other ways of making container 10 will be known to those of skill in the art and are within the scope of the present disclosure.
  • container wall 12 includes an outer surface 17 and an inner surface 13 which contacts the blood component stored in the container.
  • the container wall may be a single-layered sheet of the polymeric composition described herein.
  • container wall 12 may be made of a multiple sheet laminate wherein inner surface 13 is made of one material and outer surface 17 is made of a different material.
  • inner surface or inner sheet of a laminate may be made of PVC plasticized with a mixed plasticizer system as described herein, while outer surface 17 (or sheet) may be made of a different material.
  • container 10 may include one or more access ports 16 for connection with tubing 22, docking devices and the like to establish flow into and out from the interior chamber 15 of container 10.
  • Access ports 16 and/or tubing 22 may likewise be made of a PVC material plasticized with a mixed plasticizer system of the type described herein.
  • tubing 22 and access ports 16 may be made of PVC plasticized with a single plasticizer or a blend of leaching and/or non-leaching plasticizers.
  • containers of the type described herein may have a container sheet (wall) thickness of between approximately 0.010 to 0.018 inches.
  • the sheets may include a non-smooth or any surface finish that minimizes sheet sticking.
  • containers of the type described herein may have a container volume (i.e., interior chamber volume) of approximately 150 ml to 4 L.
  • the containers of the present disclosure are preferably sterilized by autoclaving and such autoclavable containers may typically have a 70-85 durometer (Shore A).
  • the polymeric material that makes up the container walls and, optionally, ports and/or tubing that interconnects the containers of fluid circuit may be preferably made from or otherwise include polyvinyl chloride that has been plasticized with a mixture of plasticizers as will be described in greater detail below.
  • the polymeric materials with a mixture of plasticizers described below are used at least in the walls of the storage container and specifically the interior surfaces of the walls that are in contact with the blood product or component.
  • selected plasticizers have been found to leach from the polymeric material of the walls into the stored blood component or blood product and provide support to the cellular membrane and further, in the case of red blood cells, suppress hemolysis of the red blood cells.
  • Plasticizers must be compatible with the PVC or the non-PVC material.
  • the level of plasticizer required may be much lower than for PVC as the hemolysis reduction is, in part, related to the amount of plasticizer that leaches from the polymer and not strictly the amount of plasticizer contained in the polymer. Desired leaching levels into the blood may be in the range of 5 to 50 ppm after 42 day RBC storage at 2 to 8 °C.
  • the mixture of plasticizers may have a leaching rate and an anti-hemolytic effect comparable to DEHP -- the best known and currently most widely used plasticizer in blood bag applications.
  • DEHP di-2-ethylhexylphthalate
  • Polymeric compositions made from PVC plasticized with DEHP as the primary plasticizer provide hemolysis suppression at low leaching levels.
  • plasticizers have been found to provide hemolysis suppression in red blood cells through leaching from container walls made of a polymeric material, typically but not exclusively, PVC.
  • One such plasticizer is 1,2-cyclohexane dicarboxylic acid diisononyl ester or "DINCH.”
  • DINCH is commercially available from e.g. BASF (Ludwigshafen, Germany under the product name Hexamoll®.)
  • PVC formulations plasticized with DINCH for use in blood storage containers are disclosed in U.S. Patent No. 9,993,389 , assigned to the assignee of the present application, and U.S. Patent Application Publication No.: 2017/0172847 .
  • the contents of both U.S. Patent No. 9,993,389 and U.S. Patent Application Publication No.: 2017/0172847 are disclosed in U.S. Patent No. 9,993,389 , assigned to the assignee of the present application.
  • a further alternative plasticizer that has also been found to suppress hemolysis in red blood cells is the terephthalate ester, di-2-ethyl hexyl terephthalate or DEHT (also referred to as di-octyl terephthalate ester or DOTP).
  • DEHT is commercially available from Eastman Chemical Co. (Kingsport, Tenn., USA under the product name Eastman 168).
  • PVC formulations plasticized with DINCH for use in blood storage containers are disclosed in U.S. Patent Application Publication 2014/0276527 assigned to the assignee of the present application, and U.S. Patent Application Publication No.: 2017/0172847 .
  • citrate esters include acetyl tributyl citrate (ATBC), acetyl trihexyl citrate (ATHC), and butyryl trihexyl citrate (BTHC), ATBC and BTHC being most preferred.
  • ATBC acetyl tributyl citrate
  • HAC acetyl trihexyl citrate
  • BTHC butyryl trihexyl citrate
  • These citrate esters are available from e.g. Vertellus Specialties Inc (Parsippany, N.J., USA; product names Citroflex® A4, A6, or B6).
  • Use of certain citrate esters (in combination with other leaching plasticizers) in blood storage containers is disclosed in the aforementioned U.S. Patent No. 9,993,389 , U.S. Patent Application Publication 2014/0276527 and U.S. Patent Application Publication No.: 2017/0172847 .
  • plasticizers are effective in suppressing hemolysis in red blood cells albeit to varying degrees and have different leaching profiles. It is desirable for stored RBCs to have a 42 day average storage hemolysis level below 0.4% (to ensure individual bags meet the regulatory requirements). Studies performed with different plasticizers (44 to 58 phr primary plasticizer) resulted in the following hemolysis results: Primary plasticizer Average percent 42 day storage hemolysis DEHP 0.28 DINCH (3 trials) 0.40, 0.63, 0.52 ATBC 0.50 BTHC 0.35 ATHC 0.44 20% ATBC / 80% DINCH (3 trials) 0.32, 0.22, 0.35 20% ATBC / 80% DEHT 0.32, 0.33
  • Emulsions were prepared by mixing equal amounts of Tween 80 and each of the plasticizers tested, namely, DINCH, DEHT, ATBC, BTHC, ATHC. 100 ⁇ l of an emulsion was added to an amount of 0.9% saline in sterile bottles. The amount of 0.9 % saline included, 70ml, 95 ml, 120 ml, 145 ml, 170 ml, 210 ml and 320 ml. The tubes were capped and shaken to form stable emulsions which were then stored in a refrigerator until time of use. For each emulsion, a 400 ⁇ L aliquot was transferred into two 15mL polypropylene test tubes.
  • test tubes Six (6) mL of well-mixed CPD/Adsol red blood cells were introduced into each test tube with the emulsion aliquot. The tubes were capped and inverted to mix. As a control, two 15 mL polypropylene test tubes containing 6.4 mL each of the well-mixed CPD/Adsol RBCs were prepared. Approximately 5 mL from the RBC unit were sampled and analyzed for total hemoglobin (g/dL), spun hematocrit (%), and plasma hemoglobin (mg/dL), per standard operating procedures. The test tubes were stored at 2°C-8°C for 42 days.
  • a mixed plasticizer system may allow for better control over leaching and the amount of plasticizer in the RBCs than with a single plasticizer, while still maintaining hemolysis suppression that is comparable to established plasticizers, such as DEHP-plasticized formulations/compositions.
  • Mixed plasticizer systems may also help reduce costs and improve processing, sealing and/or allow for different forms of sterilization.
  • Mixed plasticizer systems may also allow for storage of whole blood and blood components other than red blood cells wherein the particular ratio of plasticizers can be tailored to the storage needs of the component and even to particular groups of donors. Selecting plasticizers with different rates of leaching allows modifying the rate at which plasticizers leach into the blood. Reducing the plasticizer leaching rate may also prevent the plasticizer concentration from being too high or too low in the blood.
  • Polymeric compositions with mixed plasticizer systems in accordance with the present disclosure include, but are not limited to, mixtures of ATBC/DINCH, BTHC/DINCH, ATBC/DEHT, DEHT/DINCH, DEHT/ATHC and DEHT/BTHC. More particularly, mixed plasticizer systems in accordance with the present disclosure may include a mixture of 22% or less ATBC with 78% or more DINCH, a mixture of 25% or less ATBC with 75% or more DEHT, a mixture of DEHT and DINCH, a mixture of DEHT and ATHC, a mixture of DEHT and BTHC. The percentages expressed above represent a percentage of the total plasticizer content. In a preferred embodiment, the total plasticizer content as a percentage of the total polymeric composition may be between about 20%-45%, by weight and more preferably 28%-38%, by weight.
  • the polymeric compositions may include a mixture of extractable plasticizers of at least 75% 1, 2 cyclohexanedicarboxyylic acid diisononyyl ester and up to 25% acetyl tri-n-butyl citrate; a mixture of at least 85% 1, 2 cyclohexanedicarboxyylic acid diisononyyl ester and up to 15% acetyl tri-n-butyl citrate; a mixture of extractable plasticizers of at least 90% 1, 2 cyclohexanedicarboxylic acid diisononyl ester and up to 10 % acetyl tri-n-butyl citrate; a mixture of extractable plasticizers of at least 95% 1, 2 cyclohexanedicarboxylic acid diisononyl ester and up to 5 % acetyl tri-n-butyl citrate.
  • the percentages expressed above represent a percentage of the total plasticizer
  • the polymeric compositions may include a mixture of extractable plasticizers of about 50% 1, 2 cyclohexanedicarboxyylic acid diisononyyl ester and about 50% of about butyl tri-n-hexyl citrate; a of extractable plasticizers of at least 75% 1, 2 cyclohexanedicarboxyylic acid diisononyyl ester and up to 25% of about butyl tri-n-hexyl citrate; a mixture of extractable plasticizers of at least 90 % 1, 2 cyclohexanedicarboxyylic acid diisononyyl ester and up to 10% of about butyl tri-n-hexyl citrate.
  • plastic compositions suitable for use in blood or blood component storage containers are compositions that include a mixture of extractable plasticizers of at least 80% di-2-ethylhexyl terephthalate ester and up to 20% acetyl tri-n-butyl citrate; a mixture of plasticizers of at least 85% di-ethylhexyl terephthalate ester and up to 15% acetyl tri-n-butyl citrate; a mixture of plasticizers of at least 90% di-ethyl hexyl terephthalate ester and up to 10 % acetyl tri-n-butyl citrate; a mixture of plasticizers of at least 95% di-ethyl hexyl terephthalate ester and up to 5% acetyl tri-n-butyl citrate.
  • the percentages expressed above represent a percentage of the total plasticizer content.
  • polymeric compositions that include other mixed plasticizer combinations include polymeric compositions that include a mixture of 1, 2 cyclohexanedicarboxyylic acid diisononyyl ester and di-2-ethylhexyl terephthalate ester.
  • Further embodiments of still other mixed plasticizer systems that may be incorporated into polymeric compositions include a mixture of di-2-ethylhexyl terephthalate ester and acetyl tri-n-hexyl citrate
  • mixtures of di-2-ethylhexyl terephthalate ester with a citrate ester may include a mixture of di-2-ethylhexyl terephthalate ester and butyl tri-n-hexyl citrate;
  • the polymeric compositions used to make blood storage containers and described above may further include other additives such as stabilizers and co-stabilizers.
  • stabilizers include epoxidized vegetable oils such as epoxidized soybean oil and epoxidized linseed oil. These epoxidized vegetable oils may also provide a plasticizing effect to the polymer and are generally non-leaching or marginally leaching.
  • co-stabilizers may include metal stearates such as calcium stearates, zinc stearates, magnesium stearates which act as lubricants and aid in the processing of the polymeric materials.
  • Epoxidized vegetable oils may be present in the polymeric compositions described above in an amount of 1-10%, by weight of the composition. More particularly, epoxidized vegetable oils may be present in an amount of 3-7%, by weight.
  • the metal stearates may be present in any of the formulation in an amount of 0.1%-0.6%, by weight, of the overall composition.
  • the polymeric composition may include the following: 50/50 75/25 90/10 Material E1 E2 E3 phr phr phr PVC 100 100 100 B6 Citrate (BTHC - butyryl tri-n-hexyl citrate) 29 14.5 6 DINCH 29 43.5 52 ESO 10 10 10 CaZn stearate 0.2 0.2 0.2 Totals 168.2 168.2 168.2
  • non-limiting formulations include: E1 E2 E3 E4 PVC 100 100 100 100 DEHT 43.6 45.6 47 49.1 ATBC 11.6 10 8.3 6.7 ESO 6 6 6 6 ZN St 0.3 0.3 0.3 0.3 ATBC ratio 0.210 0.180 0.150 0.120

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EP20177110.2A 2019-05-30 2020-05-28 Blutvorratsbehälter aus polyvinylchlorid und gemischten weichmachern Pending EP3744775A1 (de)

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Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2022133291A1 (en) * 2020-12-18 2022-06-23 Fenwal, Inc. Disposable fluid circuits and containers for suppressing hemolysis in stored red blood cells

Families Citing this family (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP4285721A1 (de) 2022-06-02 2023-12-06 Fenwal, Inc. System zur verlängerten lagerung von roten blutkörperchen

Citations (4)

* Cited by examiner, † Cited by third party
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